Farmakogenetika statina

master's thesis

• Title (english): Pharmacogenetics of statins
• Author: Ivana Radman
• Mentor: Iveta Šimić (mentor)
• Committee member: Nada Božina (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Iveta Šimić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2014-03-19, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Primjena statina u posljednja dva desetljeća značajno je smanjila pobol i smrtnost od
kardiovaskularnih bolesti (KVB) koje u svojoj podlozi imaju aterosklerozu. Taj se
učinak prvenstveno temelji na smanjenju serumskog kolesterola male molekularne
mase (LDL-kolesterol) čija se razina efikasnije snižava većim dozama statina. U
brojnim studijama dokazana je korist od statina u primarnoj i sekundarnoj prevencijii
KVB, a smanjenje rizika kardiovaskularnih incidenata linearno ovisi u smanjenju
serumskog LDL-kolesterola. Međutim, postoji velika interindividualna varijabilnost u
odgovoru na terapiju statinima. Uz brojne poznate čimbenike kao što su dob, spol,
funkcija jetre i bubrega, istodobna primjena drugih lijekova, novija istraživanja
pružaju dokaze da su genetske varijacije dobrim dijelom odgovorne za razlike u
terapijskoj učinkovitosti statina. Sve donedavno farmakogenetičke studije su se
uglavnom bavile pojedinačnim genima u istraživanju ovih učinaka. Kako su studije s
ciljnim genima mogle objasniti samo mali dio opaženih varijacija s inkonzistentnim
rezultatima pristupilo se studijama cijelog genoma te je nastala nova znanost –
farmakogenomika. Akumulacija spoznaja o povezanosti genoma s bolestima i
interakciji genoma i lijekova vodi prema personaliziranoj medicini koja je usmjerena k
pojedinoj osobi primjenom preventivnih i prediktivnih DNA biljega.
Cilj ovog rada je dati pregled spoznaja o farmakogenetici statina, rezultate studija
cijeloga genoma i perspektive razvoja farmakogenomike i individualizirane medicine.

Abstract (english)

Over the last two decades the incidence and mortality of cardiovascular diseases
(CVD) have been significantly lowered by use of statins. Low density lipoprotein
(LDL) cholesterol is the main goal of statin therapy which efficacy is dose dependent.
The results of many studies have shown benefits of statins in primary and secondary
prevention of CVD and linear relationship between risk reduction of cardiovascular
events and serum cholesterol rate lowering have been observed. However, there is
large interindividual variability in response to statin therapy. There are many factors
involved in variations in lipid responses to statins such as age, gender, renal and
hepatic function and interaction with other drugs. The results of recent studies have
shown genetic variations as a key role player in variability of statin responses.
Until recently, pharmacogenetic studies have used mainly candidate gene
approaches to investigate these effects. Since candidate gene studies explain only a
small part of the observed variation and results have often been inconsistent,
genome-wide association (GWA) studies have been introduced giving birth to
pharmacogenomics. Accumulation of knowledge on genom-disease and genomedrug
interactions leads to personalized medicine focused to individual person by use
of preventive and predictive DNA markers.
The aims of this review are to present facts on phamacogenetics of statins, results of
GWA studies and future perspectives on pharmacogenomics and its translation into
individualized medicine.

• Keywords: hiperkolesterolemija; statini; farmakogenetika; farmakogenomika
• Keywords (english): hiperkolesterolemija; statini; farmakogenetika; farmakogenomika
• Language: croatian
• URN:NBN: urn:nbn:hr:105:541077
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2015-12-16 10:22:03